Human skin fibroblasts: From mesodermal to hepatocyte-like differentiation.

@article{citeulike:2242742, abstract = {The phenotypic homology of fibroblasts and mesenchymal stem cells (MSCs) has been recently described. Our study investigated the in vitro potential of human skin fibroblasts to differentiate into mesodermal (osteocyte and adipocyte) and endodermal (hepatocyte) cell lineages by comparison with human bone marrow (hBM) MSCs. The endodermal potential of fibroblasts was then explored in vivo in a mouse model of liver injury. Fibroblasts were able to acquire osteocyte and adipocyte phenotypes as assessed by cytochemistry and gene expression analyses. After exposure to a specific differentiation cocktail, these cells presented hepatocyte-like morphology and acquired liver-specific markers on protein and gene expression levels. Furthermore, these fibroblast-derived hepatocyte-like cells (FDHLCs) displayed the ability to store glycogen and synthesize small amounts of urea. By gene expression analysis, we observed that fibroblasts remained in a mesenchymal-epithelial transition state after hepatocyte differentiation. Moreover, FDHLCs lost their hepatocyte-like phenotype after dedifferentiation. In vivo, human fibroblasts infused directly into the liver of hepatectomized severe combined immunodeficient (SCID) mice engrafted in situ and expressed hepatocyte markers (albumin, alpha-fetoprotein, and cytokeratin 18) together with the mesodermal marker fibronectin. Despite lower liver-specific marker expression, the in vitro and in vivo differentiation profile of fibroblasts was comparable to that of mesenchymal-derived hepatocyte-like cells (MDHLCs). In conclusion, our work demonstrates that human skin fibroblasts are able to display mesodermal and endodermal differentiation capacities and provides arguments that these cells share MSCs features both on the phenotypic and functional levels.}, address = {Universit\'{e} Catholique de Louvain et Cliniques Universitaires Saint Luc, HPED Department, PEDI Unit, Laboratory of Pediatric Hepatology and Cell Therapy, 1200 Brussels, Belgium.}, author = {Lysy, P. A. and Smets, F. and Sibille, C. and Najimi, M. and Sokal, E. M. }, citeulike-article-id = {2242742}, doi = {10.1002/hep.28139}, issn = {1527-3350}, journal = {Hepatology}, month = {November}, number = {5}, pages = {1574--1585}, posted-at = {2008-01-17 04:35:56}, priority = {2}, title = {Human skin fibroblasts: From mesodermal to hepatocyte-like differentiation.}, url = {http://dx.doi.org/10.1002/hep.28139}, volume = {46}, year = {2007} }

TY - JOUR ID - citeulike:2242742 L3 - citeulike-article-id:2242742 TI - Human skin fibroblasts: From mesodermal to hepatocyte-like differentiation. JF - Hepatology VL - 46 IS - 5 SP - 1574 EP - 1585 AD - Université Catholique de Louvain et Cliniques Universitaires Saint Luc, HPED Department, PEDI Unit, Laboratory of Pediatric Hepatology and Cell Therapy, 1200 Brussels, Belgium. SN - 1527-3350 N2 - The phenotypic homology of fibroblasts and mesenchymal stem cells (MSCs) has been recently described. Our study investigated the in vitro potential of human skin fibroblasts to differentiate into mesodermal (osteocyte and adipocyte) and endodermal (hepatocyte) cell lineages by comparison with human bone marrow (hBM) MSCs. The endodermal potential of fibroblasts was then explored in vivo in a mouse model of liver injury. Fibroblasts were able to acquire osteocyte and adipocyte phenotypes as assessed by cytochemistry and gene expression analyses. After exposure to a specific differentiation cocktail, these cells presented hepatocyte-like morphology and acquired liver-specific markers on protein and gene expression levels. Furthermore, these fibroblast-derived hepatocyte-like cells (FDHLCs) displayed the ability to store glycogen and synthesize small amounts of urea. By gene expression analysis, we observed that fibroblasts remained in a mesenchymal-epithelial transition state after hepatocyte differentiation. Moreover, FDHLCs lost their hepatocyte-like phenotype after dedifferentiation. In vivo, human fibroblasts infused directly into the liver of hepatectomized severe combined immunodeficient (SCID) mice engrafted in situ and expressed hepatocyte markers (albumin, alpha-fetoprotein, and cytokeratin 18) together with the mesodermal marker fibronectin. Despite lower liver-specific marker expression, the in vitro and in vivo differentiation profile of fibroblasts was comparable to that of mesenchymal-derived hepatocyte-like cells (MDHLCs). In conclusion, our work demonstrates that human skin fibroblasts are able to display mesodermal and endodermal differentiation capacities and provides arguments that these cells share MSCs features both on the phenotypic and functional levels. AU - Lysy, PA AU - Smets, F AU - Sibille, C AU - Najimi, M AU - Sokal, EM PY - 2007/11// UR - http://dx.doi.org/10.1002/hep.28139 ER -